Taurine and isethionic acid have been shown to regulate certain aspects of excitation-contraction coupling in cardiac muscle. Other physiological effects have also been attributed to these metabolites. Isethionic acid is formed from taurine in the heart, but little else is known about this pathway. In order to clarify certain of its physiological effects, a complete understanding of the pathway is necessary. We propose to examine the control of this pathway using enzyme preparations as well as perfused heart. This investigator has already observed that taurine is converted to sulfoacetaldehyde by rat heart homogenates. The further reduction of sulfoacetaldehyde to isethionic acid remains to be studied. Heart homogenates will be incubated with sulfoacetaldehyde and, after protein precipitation, subjected to paper chromatography and electrophoresis for identification of isethionic acid. The enzymes catalyzing these reactions will be purified by standard techniques: solubilization, ammonium sulfate fractionation, and a series of ion exchange and molecular sieve chromatographic steps. Enzyme kinetics on the pure enzyme will be examined to elucidate possible controlling factors. The enzyme preparations will ultimately be used in in vivo studies to measure intracellular levels of taurine, sulfoacetadehyde and isethionic acid. This information is invaluable in determining the control points in the pathway. As a prelude to undertaking metabolic studies in perfused rat heart, the effect of taurine upon cardiac contractility will be examined. Typical dose-response curves of cardiac work versus taurine concentration will be obtained. The relationship of the taurine effect and the calcium cycle will be examined.